Natural Killer Cells may Exert Antidepressant-like Effects in Mice by Controlling the Release of Inflammatory Factors

Depression or stress is reportedly related to the overflow of inflammatory factors in the body and T cells were reported to play important roles in balancing the release of inflammatory factors through vagus nerve circuit. However, few works have been conducted to find if natural killer (NK) cells can also exert the similar function in the reported vagus nerve circuit as T cells and if there was any relationship between depression and this function. In the present study, the behavioral tests on BALB/c mice indicated that the depressant-like symptoms could be improved and simultaneously the concentrations of inflammatory factors in peripheral blood could be reduced significantly by adoptively transferring NK cells into stressed BALB/c mice. The results revealed that NK cells could control the release of inflammatory factors secreted by macrophages and β₂-AR (β₂-adrenergic receptor) on the NK cells were of great importance. Behavioral tests on NCG mice indicated that the antidepressant-like effects of NK cells notably declined after adoptively transferring NK cells with β₂-AR deficiency or with ChAT (choline acetyltransferase) deficiency into stressed NCG mice. Simultaneously, the anti-inflammatory effects also declined significantly both in vivo and in vitro, which indicated that the antidepressant-like property of NK cells may be related to its ability of controlling the release of inflammatory factors. Taken together, we find that NK cells may balance the release of inflammatory factors in our body by transporting the information between the terminal vagal branches and macrophages, which is the mechanism that NK cells may exert antidepressant-like effects.